tbuckley/cabot-search huggingface dataset:
Bevacizumab combined with atezolizumab or sintilimab as second-line treatment in patients with advanced hepatocellular carcinoma: A retrospective study.
Authors: Leijuan Gan, Huikai Li, Qiang Wu, Qiang Li, Yunlong Cui, Wei Zhang, Feng Fang, Wei Lu, Guangtao Li, Shaohua Ren, Yayue Liu, Mengran Lang, Ruyu Han, Tianqiang Song
Journal: Journal of Clinical Oncology (2023)

544 Background: The combination of bevacizumab and immune checkpoint inhibitors (ICI) has demonstrated promising efficacy and safety in the first-line treatment of advanced hepatocellular carcinoma (HCC). However, this combination has not been examined in patients with previous first-line treatment of ICI and tyrosine kinase inhibitor. This study aimed to investigate the effectiveness and safety of bevacizumab combined with atezolizumab or sintilimab as second-line treatment in patients with advanced HCC. Methods: The retrospective study included patients with advanced HCC who received combined therapy of bevacizumab and atezolizumab or sintilimab after failure of lenvatinib plus ICI between July 28, 2020 and March 7, 2022. Baseline patient characteristics were collected. Treatment response, overall response rate (ORR) and disease control rate (DCR) were evaluated according to response evaluation criteria in solid tumors (RECIST) version 1.1. Overall survival (OS) and progression-free survival (PFS) were analyzed by the Kaplan-Meier method. Treatment-related adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Results: A total of 20 patients with advanced HCC were included, with a median follow-up time of 11.05 (5.03-20.63) months. Eleven patients died by the last follow-up on August 12, 2022. There were 18 males (90%) and two females (10%). The average age was 59.9±12.08 years. Seven patients (35%) had distant metastasis, and nine (45%) had vascular invasion. Liver function was classified as Child-Pugh grade A in 17 patients (85%) and grade B in three (15%). Patients with Barcelona Clinic Liver Cancer (BCLC) stages B, C and D were 1 (5%), 16 (80%) and 3 (15%), respectively. Eighteen patients (90%) had previous topical therapy. Of all patients previously administered lenvatinib plus ICI as first-line treatment, 14 (70%) had PFS longer than three months. ORR and DCR were 15% (95% confidence interval [CI], 3.2-37.9) and 55% (95% CI, 31.5-76.9), respectively. Median OS was 8.00 months (95% CI, 0.00-16.66), while median PFS was 3.80 months (95% CI, 2.41-5.19). Adverse events were observed in 14 patients (70%). Adverse events of grade 3 or worse occurred in six patients (30%). Conclusions: The combination of bevacizumab with atezolizumab or sintilimab had tolerable safety profile but poor response in the second-line treatment of HCC. Despite the satisfying efficacy as first-line therapy, this combination is not a cost-effective recommendation for advanced HCC cases who failed the first-line treatment of lenvatinib plus ICI. [Table: see text]
Sorafenib plus tislelizumab as maintenance therapy for patients with advanced hepatocellular carcinoma treated with transarterial chemoembolization: A phase II study.
Authors: Mingyue Cai, Xiaoyang Hong, Wensou Huang, Yongjian Guo, Wenbo Shi, Licong Liang, Jingwen Zhou, Liteng Lin, Ye Chen, Kangshun Zhu
Journal: Journal of Clinical Oncology (2023)

574 Background: Tyrosine kinase inhibitor combined with immune checkpoint inhibitor has been reported to confer a survival benefit in patients with unresectable hepatocellular carcinoma (HCC). This phase II study (NCT04599777) aimed to evaluate the safety and efficacy of sorafenib plus tislelizumab (Sor-Tis) for patients with advanced HCC who received transarterial chemoembolization (TACE). Methods: The key inclusion criteria were: age ≥ 18 years; BCLC C stage HCC; no prior systemic therapy; Child-Pugh score ≤7; ECOG PS ≤1. The key exclusion criteria were: tumor thrombus involving the main portal vein or vena cava; central nervous system metastasis; history of malignancies other than HCC; history of organ and stem cell transplantation. Sorafenib (400 mg Bid) and tislelizumab (200 mg Q3W) was started at 3-7 days after the first TACE (TACE was repeated on demand). The primary endpoint was overall survival (OS). The secondary endpoints included treatment-related adverse events (TRAEs), progression free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Results: Thirty patients were enrolled in this study. Among these patients, 27 (90.0%) had macrovascular invasion, 12 (40.0%) had extrahepatic metastasis and 14 (46.7%) had intrahepatic tumor number &gt;3. The mean largest tumor diameter was 11.4±3.9 cm. Till cutoff date (September 15 th , 2022), the mean follow-up for the patients was 16.6±3.8 months. The median OS was not reached. The ORR per RECIST 1.1 and mRECIST was 20.0% and 53.3%, respectively. The DCR per RECIST 1.1 or mRECIST was 86.7%. During follow-up, 29 patients (96.7%) experienced disease progression (per RECIST 1.1 or mRECIST). The median PFS was 6.8 (95% confidence interval [CI] 4.5-9.0) months. TRAEs occurred in 28 patients (93.3%) and ≥grade 3 TRAEs was observed in 11 patients (36.7%). There was no treatment-related death in these patients. Conclusions: Sor-Tis showed preliminary clinical benefits and was tolerated in advanced HCC patients treated with TACE. This study is still ongoing and further follow-up is required to obtain final survival results. Clinical trial information: NCT04599777 .
Late Health Outcomes Among Survivors of Wilms Tumor Diagnosed Over Three Decades: A Report From the Childhood Cancer Survivor Study
Authors: Brent R. Weil, Andrew J. Murphy, Qi Liu, Rebecca M. Howell, Susan A. Smith, Christopher B. Weldon, Elizabeth A. Mullen, Arin L. Madenci, Wendy M. Leisenring, Joseph P. Neglia, Lucie M. Turcotte, Kevin C. Oeffinger, Amanda M. Termuhlen, Sogol Mostoufi-Moab, Jennifer M. Levine, Kevin R. Krull, Yutaka Yasui, Leslie L. Robison, Gregory T. Armstrong, Eric J. Chow, Saro H. Armenian
Journal: Journal of Clinical Oncology (2023)

To evaluate long-term morbidity and mortality among unilateral, nonsyndromic Wilms tumor (WT) survivors according to conventional treatment regimens.
Incidence and costs associated with clinically significant events in real-world patients with unresectable hepatocellular carcinoma on systemic therapy.
Authors: Marcus Healey, Daniel Simmons, Stephen J Valerio, Janvi Sah, Debra Pierce, Zhuoxin Jiang, Darren Thomas, Jesica Levingston Mac Leod, Yian Lin
Journal: Journal of Clinical Oncology (2023)

514 Background: First-line (1L) treatments for unresectable HCC (uHCC) include atezolizumab plus bevacizumab (ATEZO+BEV), and the tyrosine kinase inhibitors (TKIs) sorafenib (SOR) and lenvatinib (LEN). In clinical trials, these therapies were associated with clinically significant events (CSEs): bleeding, clotting, encephalopathy, and portal hypertension. The objective of this study was to evaluate the real-world incidence of these CSEs and their impact on healthcare resource utilization (HCRU) and costs in patients with uHCC receiving ATEZO+BEV or a TKI. Methods: We conducted a retrospective, observational, cohort study using Clinformatics Data Mart to characterize 1379 US patients diagnosed with uHCC between January 2007 and June 2021 who received treatment with ATEZO+BEV (n=271) or a TKI (SOR, n=891; LEN, n=217). Incidence of the selected CSEs was evaluated as incident cases per 100-person-years (PY) of treatment. Descriptive statistics assessed patient characteristics, HCRU, and medical costs. Results: Mean age at diagnosis was 67.7 years; most patients were male (76.1%), white (52.4%), and had Medicare (74.2%); these characteristics were consistent across treatment groups. While on ATEZO+BEV, SOR or LEN, 147 (54.2%), 481 (54.0%), and 121 (55.8%) patients experienced ≥1 CSEs, respectively. For the ATEZO+BEV group, the most common CSEs were clotting (61.2 cases/100-PY [95% confidence interval {CI}: 45.1, 81.1]) and bleeding (55.4 [40.3, 74.4]). For the SOR group the most common CSEs were encephalopathy (54.5 [46.9, 63.1]) and clotting events (51.3 [44.1, 59.4]), for the LEN group the most common CSEs were clotting events (63.5 [47.4, 83.3]) and encephalopathy (56.7 [42.2, 74.5]). Overall, mean HCRU was high in the outpatient visits, while increases in the cohorts and among events (e.g., for surgery and inpatient visits) were seen in patients with ≥1 CSEs versus those without CSEs. Mean monthly medical costs were also substantially higher with ≥1 CSEs (Table). Conclusions: There were high levels of CSEs in patients receiving ATEZO+BEV or TKIs for 1L uHCC, and the occurrence of these events is associated with an economic burden to the healthcare system. Safety should continue to be monitored for patients treated for uHCC and new therapy options with reduced risks for developing CSEs are needed. [Table: see text]
Genomic analysis to elucidate similarities and differences between primary colorectal cancers and colorectal cancer liver metastases.
Authors: Steven Allen Buechler
Journal: Journal of Clinical Oncology (2023)

25 Background: Whole transcriptome (WT) analysis of primary colorectal cancer (pCRC) has shown that the tumor microenvironment (TME) plays a critical role in disease progression and response to treatment. Colorectal cancer liver metastases (CRCLM) bear many genetic similarities to primary tumors, however differences in the microenvironment could effect drug response. Since 80% of metastatic CRC patients have liver metastases there is a critical need for further molecular analysis of CRCLM. Methods: Using a novel method to identify aberrant activity of signaling pathways, continuous scores (called pathway cluster scores, PCS) were derived from subsets of Hallmark gene sets of MSigDB. PCS scores that were prognostic in CRCLM were considered relevant to disease progression. Combined studies of such scores in CRCLM and pCRC were used to explore differing effects of the colon and liver TMEs. Analyses were performed on published WT datasets of pCRC (4 cohorts, n = 2,978) and CRCLM (3 cohorts, n = 498). Immune cell infiltration levels were estimated with Immunedeconv. Results: The most significantly prognostic PCS score in CRCLM cohort GSE159216 (n = 171) was one derived from a cluster of 28 KRAS signaling genes, called K-score (p = .0004). Subtypes K+ (good prognosis) and K- (poor prognosis) denote samples with K-score above, respectively below, the median. Gene set enrichment analysis showed that in all CRCLM cohorts, K- was enriched versus (v) K+ in proliferation-related pathways, e.g. E2F signaling and DNA Repair, while K+ was enriched v K- in multiple immune system pathways. In both CRCLM cohorts, K+ was enriched v K- in infiltration of neutrophils and CD4+ T cells, while infiltration levels of CD8+ T cell were not significantly different between K+ and K-. The T cell homing chemokines CXCL12, CCL19, CCL21 were elevated in K+ v K-. The aforementioned molecular features of K+ and K- also held in all pCRC cohorts; however in these cohorts, K+ was also enriched v K- in B cell and M2 macrophage infiltration. Also, in pCRC expression of the B cell attractor CXCL13 and biomarkers for tertiary lymphoid structures (TLS) were significantly elevated in K+ v K-. Of note, TLS have been associated with response to immune checkpoint inhibitors in multiple cancer types. In addition, in 18 pairs of matching pCRC and CRCLM samples (GSE49355), K-scores of pCRC samples were significantly correlated to K-scores of the matching CRCLM samples (p = .01). Chemokine expression levels differed in matching pairs: mean expression of CXCL12 was significantly higher in CRCLM than pCRC, while mean expression of CXCL13 was significantly higher in pCRC than CRCLM. Conclusions: In the study cohorts, K- tumors in both pCRC and CRCLM, were proliferative and lacked inflammation. However, while both pCRC and CRCLM K+ tumors were inflamed and enriched with CD4+ T cells, only pCRC K+ tumors were likely to contain TLS.
Clinical benefit of granulocyte-colony stimulating factor (GCSF) use during chemoimmunotherapy treatment for metastatic pancreatic adenocarcinoma (mPDAC).
Authors: Jaclyn P. Lyman, Christopher R Cabanski, Stephen Maddock, Robert A. Wolff, Zev A. Wainberg, Andrew H. Ko, Osama E. Rahma, George A. Fisher, Peter Edward Gabriel, Abigail Doucette, Binbin Zheng-Lin, Molly A. Maloy, Ute Dugan, Justin P. Fairchild, Marko Spasic, Jill O'Donnell-Tormey, Robert H. Vonderheide, Mark H. O'Hara, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2023)

757 Background: GCSF is used for primary/secondary prophylaxis of chemotherapy(chemo)-associated neutropenia in patients (pts) with mPDAC. GCSF may also increase the populations of healthy, naïve immune cells in an otherwise immunologically dysregulated and cold environment, potentially augmenting therapy outcome with immunomodulatory (IO) agents. Here, we describe the impact of GCSF administration on OS, PFS, and time on treatment (TOT) in the setting of mPDAC for (1) a trial in which pts were administered chemo-IO combinations and (2) a synthetic control arm using retrospective real-world data from pts who received standard-of-care (SOC) chemo (PASCAL). Methods: PRINCE is a ph1b/2 study evaluating gemcitabine (gem) and nab-paclitaxel (NP) ± sotigalimab (sotiga; CD40 agonist) ± nivolumab (nivo; anti-PD1) for pts with mPDAC (NCT0324250), where prophylactic GCSF use was prohibited. PASCAL pts received SOC gem/NP and primary/secondary GCSF use was allowed. In this retrospective analysis, GCSF use was defined as receiving at least 1 dose of GCSF anytime during treatment. OS, PFS, and TOT and associated HRs and CIs were calculated using Kaplan-Meier and Cox methods. PFS data not available for PASCAL. Results: 32/123 (26%) and 16/68 (24%) pts received GCSF in PRINCE and PASCAL, with 84% and 88% of pts receiving at least 1 dose within the first 3 cycles, respectively. In PRINCE, GCSF use was associated with significant improvements in OS (HR [95% CI]: 0.62 [0.40-0.97]), PFS (0.71 [0.47-1.08]), and TOT (0.67 [0.45-1.01]). These improvements were most notable in the sotiga-containing arms (table). In the absence of IO treatment, however, no statistical significance was observed in PASCAL (HR [95% CI]: OS = 0.81 [0.44-1.51]; TOT = 0.90 [0.51-1.58]). Additional work is ongoing to understand the association of GCSF usage with known prognostic factors. Conclusions: These analyses suggest that GCSF use may enhance the clinical benefits of chemo-IO in mPDAC. These potential benefits of GCSF usage warrant further evaluation in other chemo-IO trials as well as prospective evaluation in pre-clinical and clinical settings. Clinical trial information: NCT03214250 . [Table: see text]
Primary percutaneous stenting above the ampulla for palliative biliary drainage of malignant hilar biliary obstruction.
Authors: Stijn Franssen, Lydi M.J.W. Van Driel, Adriaan Moelker, Bas Groot Koerkamp
Journal: Journal of Clinical Oncology (2023)

527 Background: Most patients with malignant hilar biliary obstruction (MHBO) are ineligible for surgical resection due to distant metastasis, locally advanced disease, or poor performance status. These patients mostly undergo biliary drainage with endoscopic stents or percutaneous drains that cross the ampulla. This approach causes bacterial colonization of the bile ducts, recurrent cholangitis, and biliary reinterventions. Few patients become eligible for palliative systemic chemotherapy, because of inadequate drainage and drainage-related complications. The solution is primary percutaneous stenting (PPS) with one or more fenestrated self-expandable metal stent (SEMS) across the biliary obstruction, without crossing the ampulla. After PPS, the percutaneous transhepatic puncture tract is sealed with glue without leaving an external biliary drain. The aim of this study was to assess the safety, feasibility, and effectiveness of PPS in patients with unresectable MHBO. Methods: A single center prospective study was performed from October 2020 till September 2022 including 35 patients with MHBO who underwent PPS. We made a comparison with a historical cohort of 90 consecutive patients treated with primary endoscopic biliary drainage at our center from 2011 till 2020. Results: All 35 patients had technical successful percutaneous SEMS placement. Perihilar cholangiocarcinoma was present in 15 patients (43%), intrahepatic cholangiocarcinoma in 14 patients (40%), and gallbladder cancer in 6 patients (17%). Two patients required two attempts because the stricture could not be passed at the first attempt. Two patients developed cholecystitis and one patient had melaena due to intrahepatic bleeding of a portal venous branch requiring blood transfusion. One patient (3%) developed cholangitis after the first biliary drainage procedure because the tumor extended up to the ampulla, requiring additional stenting. No cholangitis was seen in the other 34 patients. We made a comparison with a historical cohort of 90 consecutive patients treated with primary endoscopic biliary drainage at our center from 2011 till 2020. Only 3 patients (9%) required a readmission and 3 patients (9%) a reintervention. Palliative systemic chemotherapy was administered in 26 patients (75%) versus 18 patients (20%) after primary endoscopic biliary drainage. The median overall survival was 10.6 months (95% CI 8.1 – not reached) versus 4.3 months (95% CI 3.1 – 6.4) after primary endoscopic biliary drainage. After PPS, no patients died because of cholangitis or drainage-related complications. Conclusions: Primary percutaneous stenting with fenestrated SEMS without crossing the ampulla is safe, feasible, and effective for palliative treatment of patients with MHBO. These promising results need to be confirmed in a randomized controlled trial. Clinical trial information: NL9624 .
A sequential therapy with sorafenib followed by regorafenib against single-line atezolizumab and bevacizumab in advanced hepatocellular carcinoma (HCC): Indirect treatment comparisons (ITC) using the RESORCE study.
Authors: Jamie Partridge, David Aceituno, Noman Paracha, Howard Thom
Journal: Journal of Clinical Oncology (2023)

537 Background: Our objective was to explore ITC of sequential therapy with sorafenib followed by regorafenib (sorego) against atezolizumab+bevacizumab (atezobev) in HCC. Naïvely comparing median Overall Survival (OS) from sorafenib initiation on sorego in the RESORCE trial with atezobev from IMbrave150 is biased by population imbalance and selection of patients who survived on sorafenib in RESORCE. We used unanchored Matching Adjusted Indirect Comparison (MAIC) and novel survivorship bias adjusted anchored ITC (SBITC) to overcome these limitations. Methods: Overall Survival (OS) from sorafenib initiation in RESORCE on sorego were compared with reconstructed Individual Patient Data (IPD) OS based on Kaplan-Meier curves from IMbrave150 on atezobev. In MAIC, the sorego arm of RESORCE was weighted on reported baseline characteristics to match the IMbrave150 atezobev arm. In SBITC, sorafenib IPD from IMbrave150 were sampled with replacement and added to the RESORCE BSC arm to correct for “survivorship bias”. Sample size was sufficient for follow-up prior to RESORCE randomisation to be within 5% of sorafenib follow-up in IMbrave150. Anchored Bucher ITC was used to compare to unadjusted IMbrave150 with bootstrapping to obtain standard errors. Hazard Ratios (HRs) were used to compare OS. Results: MAIC gave an OS HR of 0.75 (95% confidence interval 0.60, 0.93; p-value=0.007). Effective sample size (ESS) was reduced from 379 to 271.75. SBITC gave a HR of 0.63 (0.52, 0.76; p-value &lt;0.001) requiring an average of 83 sorafenib patients to be added from IMbrave150. Conclusions: We proposed MAIC and SBITC to overcome biases in naïve comparisons of OS on sorego with atezobev in HCC. However, MAIC is limited to baseline characteristics in IMbrave150 and does not adjust for “survivorship bias”. SBITC depends on sample size from IMbrave150, and makes no adjustment for imbalance in baseline characteristics. Despite these limitations, our methods were consistent with naïve comparisons and suggested longer OS with sorego compared to atezobev in patients with HCC.
Efficacy and safety of envafolimab plus lenvatinib combined with TACE in unresectable hepatocellular carcinoma: An open-label, single-arm, phase 2 study—The CISLD-12 study.
Authors: Tingbo Liang, Yiwen Chen, Xin Huang, Wendi Hu, Xiang Li, Junhui Sun, Yan Shen, Min Zhang, Jian Wu, Shunliang Gao, Jun Yu, Risheng Que, Yun Zhang, Fuchun Yang, Weiliang Xia, Aibin Zhang, Xiaofeng Tang, Xueli Bai
Journal: Journal of Clinical Oncology (2023)

558 Background: Transarterial chemoembolization (TACE) is one of the standard treatments for patients with intermediate-stage hepatocellular carcinoma (HCC). The combination of immune checkpoint inhibitors (ICIs) and lenvatinib has shown to be an effective regimen in patients with unresectable HCC (uHCC). In this study, we aim to investigate the efficacy and safety of combination of Envafolimab (a novel, single-domain PD-L1 antibody) with Lenvatinib plus TACE in uHCC patients. Methods: This is a prospective, open-label, single-arm, phase 2 study. Adults with confirmed uHCC with BCLC stage B or C, Eastern Cooperative Oncology Group performance status 0 or 1, Child–Pugh scored ≤7 and no previous systemic treatment for HCC are eligible. Patients will receive Lenvatinib once daily plus Envafolimab every 3 weeks plus TACE. TACE will be conducted repeatedly every 6 weeks on demand according to investigators’ consideration, mainly based on the proportion of viable tumors. Imaging evaluation will be conducted every 6 weeks. The primary endpoint is objective response rate (ORR). Disease control rate (DCR), duration of response (DoR), progression free survival (PFS), overall survival (OS) and safety are evaluated as secondary endpoints (NCT05213221). Results: forty patients were consecutively enrolled from March, 2022 to September 2022. The median age was 54.5 years. At present, thirty-six patients were included for efficacy analysis, and forty for safety evaluation. Number of patients with BCLC stage B and C was 17(47.2%) and 19 (52.8%), respectively. 13 (36.1%) patients presented with portal vein tumor thrombus (PVTT) and 2 (5.6%) patient presented with hepatic vein tumor thrombus (HVTT). The ORR was 36.1% and 80.6%, and DCR was 77.8% and 83.3%, based on RECIST v1.1 and modified RECIST respectively. 11 patients reached the standard of conversion to resectable HCC and received radical resection. The most common TRAEs were elevated AST (75%), elevated ALT (65%) and leukopenia (42.5%). No treatment-related deaths occurred. The survival data are not mature at present. Conclusions: Envafolimab plus Lenvatinib combined with TACE is a promising and tolerable therapeutic regimen for patients with BCLC B/C unresectable HCC. Clinical trial information: NCT05213221 .